BACKGROUND Aortic stenosis (AS) and mitral regurgitation (MR) result in different patterns of left ventricular remodeling and hypertrophy. OBJECTIVES We characterized left ventricular wall stress (LVWS) profiles in pressure and volume-overloaded systems, examined the relationship between baseline LVWS and cardiac remodeling, and assessed the acute effects of valve intervention on LVWS using invasive pressures combined with cardiac magnetic resonance (CMR) imaging measures of left ventricular volumes/mass. METHODS A total of 47 patients with severe AS undergoing transcatheter aortic valve replacement (TAVR) and 15 patients with severe MR undergoing MitraClip (MC) underwent a 6-minute walk test (6MWT), transthoracic echocardiogram, and CMR before their procedures. Catheters in the left ventricle were used to record hemodynamic changes before and after valve/clip deployment. This was integrated with CMR data to calculate LVWS before and after intervention. RESULTS The TAVR group demonstrated significant reductions in systolic LVWS post procedure (median 24.7 Pa [IQR: 14 Pa] pre vs median 17.3 Pa [IQR: 12 Pa] post; P < 0.001). The MC group demonstrated significant reductions in diastolic LVWS (median 6.4 Pa [IQR: 5 Pa] pre vs median 4.3 Pa [IQR: 4.1 Pa] post; P = 0.021) with no significant change in systolic LVWS (30.6 +/- 1.61 pre vs 33 +/- 2.47 Pa post; P = 0.16). There was an inverse correlation between baseline systolic LVWS and 6MWT in the TAVR group (r = -0.31; P = 0.04). CONCLUSIONS TAVR results in significant reductions in systolic LVWS acutely. MC results in significant reductions in diastolic LVWS. Higher baseline systolic LVWS in TAVR is associated with shorter 6MWT suggesting that in AS, LVWS may be a useful marker of early decompensation. (c) 2024 by the American College of Cardiology Foundation.

Abstract Background Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by diffuse, multifocal segmental narrowing of cerebral arteries and can result in ischaemic stroke. Causal factors, identified in 60% of cases, include immunosuppressant pharmacotherapy. The few reports following heart transplantation are almost all in Asian recipients. We report on a Caucasian Australian patient with immunotherapy induced RCVS post heart transplantation to highlight the state of knowledge of the condition and the treatment dilemma it poses. Case presentation A 51-year-old female underwent orthotopic heart transplantation at our institution. Induction immunotherapy comprised basiliximab, mycophenolate mofetil and methylprednisolone. On day 6 post-transplantation the patient was transitioned to oral prednisolone and tacrolimus. On day 7 the patient began to experience bilateral, severe, transient occipital and temporal headaches. On day 9 tacrolimus dose was up-titrated. A non-contrast computed tomography brain (CTB) was normal. Endomyocardial biopsy on day 12 demonstrated moderate Acute Cellular Rejection (ACR), which was treated with intravenous methylprednisolone. That evening the patient experienced a 15-minute episode of expressive dysphasia. The following morning she became confused, aphasic, and demonstrated right sided neglect and right hemianopia. A CT cerebral perfusion scan demonstrated hypoperfusion in the left middle cerebral artery (MCA) territory and cerebral angiography revealed widespread, focal multi-segmental narrowing of the anterior and posterior circulations. A diagnosis of RCVS was made, and nimodipine was commenced. As both steroids and tacrolimus are potential triggers of RCVS, cyclosporin replaced tacrolimus and methylprednisolone dose was reduced. A further CTB demonstrated a large left MCA territory infarct with left M2 MCA occlusion. The patient made steady neurological improvement. She was discharged 34 days post-transplantation with mild residual right lower limb weakness and persistent visual field defect on verapamil, cyclosporine, everolimus, mycophenolate mofetil and prednisolone. Conclusion Reversible cerebral vasoconstriction syndrome is rare after orthotopic heart transplantation. Until now, RCVS has been almost exclusively described in Asian recipients, and is typically caused by immunotherapy. The condition may lead to permanent neurological deficits, and in the absence of definitive treatments, early recognition and imaging based diagnosis is essential to provide the opportunity to remove the causal agent(s). Co-existent ACR, can pose unique treatment difficulties.

OBJECTIVES:To describe myocarditis as an adverse event after coronavirus disease 2019 (COVID-19) vaccination, including a detailed description of clinical phenotypes and diagnostic test results and differences by age, sex, and degree of troponin level elevation. STUDY DESIGN:Retrospective cross-sectional study. SETTING, PARTICIPANTS:Cases of suspected myocarditis following the administration of a COVID-19 vaccine in Victoria during 22 February 2021 - 30 September 2022 reported to Surveillance of Adverse Events Following Vaccination In the Community (SAEFVIC), with symptom onset within 14 days of vaccination, and deemed to be confirmed myocarditis according to the Brighton Collaboration Criteria. MAIN OUTCOME MEASURES:Demographic (sex, broad age group), vaccine, and clinical presentation characteristics; cardiac investigation results (troponin levels, electrocardiography, echocardiography, cardiac magnetic resonance imaging [cMRI]). RESULTS:Of 454 SAEFVIC reports of suspected COVID-19 vaccine-associated myocarditis, 206 were deemed confirmed cases. The median age of people with confirmed myocarditis was 21 years (interquartile range [IQR], 16-32 years; range, 10-76 years); 129 were aged 24 years or younger (63%), 155 were male (75%). The median time from vaccination to symptom onset was two days (IQR, 1-4 days); 201 cases (98%) followed the administration of mRNA vaccines; five cases followed vaccination with AZD122. Forty-six cases followed first vaccine doses (22%), 138 second doses (67%), and 22 cases third vaccine doses (11.0%). In 201 cases, people initially presented to emergency departments; 129 people were admitted to hospital (63%; median length of stay, two days; IQR, 1-3 days). Five people were admitted to intensive care. Echocardiographic abnormalities were identified in 26 of 200 patients (13%); electrocardiographic abnormalities were identified in 105 of 206 patients (51%; less frequently in female than male patients: adjusted odds ratio, 0.75; 95% confidence interval, 0.64-0.89). Troponin levels were elevated in 205 of 206 patients; the median increase was greater in male (95.3-fold; IQR, 5.8-273-fold) than female patients (9.9-fold; IQR, 4.7-50-fold). No cMRI abnormalities were found in patients for whom the troponin increase was threefold or less. CONCLUSION:The clinical severity of COVID-19 vaccine-associated myocarditis in Victoria was generally mild. Markers of a more severe phenotype were more frequently recorded for male patients and people aged 24 years or younger. A threefold troponin increase could be used as a threshold for risk stratification of people with COVID-19 vaccine-associated myocarditis, especially in hospitals with limited access to cMRI facilities.

AbstractAimsElectronic health records (EHR) linked to Digital Imaging and Communications in Medicine (DICOM), biological specimens, and deep learning (DL) algorithms could potentially improve patient care through automated case detection and surveillance. We hypothesized that by applying keyword searches to routinely stored EHR, in conjunction with AI‐powered automated reading of DICOM echocardiography images and analysing biomarkers from routinely stored plasma samples, we were able to identify heart failure (HF) patients.Methods and resultsWe used EHR data between 1993 and 2021 from Tayside and Fife (~20% of the Scottish population). We implemented a keyword search strategy complemented by filtering based on International Classification of Diseases (ICD) codes and prescription data to EHR data set. We then applied DL for the automated interpretation of echocardiographic DICOM images. These methods were then integrated with the analysis of routinely stored plasma samples to identify and categorize patients into HF with reduced ejection fraction (HFrEF), HF with preserved ejection fraction (HFpEF), and controls without HF. The final diagnosis was verified through a manual review of medical records, measured natriuretic peptides in stored blood samples, and by comparing clinical outcomes among groups. In our study, we selected the patient cohort through an algorithmic workflow. This process started with 60 850 EHR data and resulted in a final cohort of 578 patients, divided into 186 controls, 236 with HFpEF, and 156 with HFrEF, after excluding individuals with mismatched data or significant valvular heart disease. The analysis of baseline characteristics revealed that compared with controls, patients with HFrEF and HFpEF were generally older, had higher BMI, and showed a greater prevalence of co‐morbidities such as diabetes, COPD, and CKD. Echocardiographic analysis, enhanced by DL, provided high coverage, and detailed insights into cardiac function, showing significant differences in parameters such as left ventricular diameter, ejection fraction, and myocardial strain among the groups. Clinical outcomes highlighted a higher risk of hospitalization and mortality for HF patients compared with controls, with particularly elevated risk ratios for both HFrEF and HFpEF groups. The concordance between the algorithmic selection of patients and manual validation demonstrated high accuracy, supporting the effectiveness of our approach in identifying and classifying HF subtypes, which could significantly impact future HF diagnosis and management strategies.ConclusionsOur study highlights the feasibility of combining keyword searches in EHR, DL automated echocardiographic interpretation, and biobank resources to identify HF subtypes.

Journal Article A Confusing Collapse: Case of an Intracranial Mass Mimicker in a Cardiac Transplant Recipient Get access Vivien Wai Yun Lai, Vivien Wai Yun Lai Department of Infectious Diseases, Alfred Hospital, Melbourne, Australia Correspondence: V. W. Y. Lai, Department of Medicine, Alfred Hospital, 55 Commercial Rd, Melbourne, VIC 3004, Australia (vivien.lai.wy@gmail.com); O. Morrissey, Department of Infectious Diseases, Alfred Hospital, 55 Commercial Rd, Melbourne, VIC 3004, Australia (O.Morrissey@alfred.org.au). https://orcid.org/0000-0003-4530-9864 Search for other works by this author on: Oxford Academic PubMed Google Scholar David Griffin, David Griffin Department of Infectious Diseases, Alfred Hospital, Melbourne, AustraliaDepartment of Infectious Diseases, Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Australia Search for other works by this author on: Oxford Academic PubMed Google Scholar Jillian Lau, Jillian Lau Department of Infectious Diseases, Alfred Hospital, Melbourne, Australia Search for other works by this author on: Oxford Academic PubMed Google Scholar Catriona McLean, Catriona McLean Department of Anatomical Pathology, Alfred Hospital, Melbourne, Australia Search for other works by this author on: Oxford Academic PubMed Google Scholar Christina Chang, Christina Chang Department of Infectious Diseases, Alfred Hospital, Melbourne, AustraliaDepartment of Infectious Diseases, Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Australia Search for other works by this author on: Oxford Academic PubMed Google Scholar Shalini Bigwood, Shalini Bigwood Department of Radiology, Alfred Hospital, Melbourne, Australia Search for other works by this author on: Oxford Academic PubMed Google Scholar James Hare, James Hare Department of Cardiology, Alfred Hospital, Melbourne, Australia Search for other works by this author on: Oxford Academic PubMed Google Scholar Orla Morrissey Orla Morrissey Department of Infectious Diseases, Alfred Hospital, Melbourne, AustraliaDepartment of Infectious Diseases, Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Australia Correspondence: V. W. Y. Lai, Department of Medicine, Alfred Hospital, 55 Commercial Rd, Melbourne, VIC 3004, Australia (vivien.lai.wy@gmail.com); O. Morrissey, Department of Infectious Diseases, Alfred Hospital, 55 Commercial Rd, Melbourne, VIC 3004, Australia (O.Morrissey@alfred.org.au). Search for other works by this author on: Oxford Academic PubMed Google Scholar Clinical Infectious Diseases, Volume 78, Issue 2, 15 February 2024, Pages 484–487, https://doi.org/10.1093/cid/ciad697 Published: 17 February 2024

Signals that inform prospective receivers of potential contingencies associated with the signaler or its environment may be innate, or may rely upon repeated association between signal production and a context relevant to the receiver, or theory of mind, such that signalers and/or receivers infer the state or contextual situation communicative partners find themselves in. While theoretical discourse on the information content of signals has focused on the coevolution of signalers and receivers as distinct entities, the fact that individuals often act both as receivers and signalers in similar communicative contexts over the course of their lives presents the possibility that signals emitted in a given context may reflect the signaler's own experience as a receiver in the same or similar contexts. This process, which we term “Exchangeability,” would allow signalers to encode appropriate information in signals and receivers to extract meaningful information without conditioning or recourse to theory of mind. We propose that Exchangeability readily accounts for the expression of true communication, where both signalers and receivers benefit, eavesdropping, where receivers alone benefit, and manipulation, where signalers benefit at the expense of receivers, thus providing a previously overlooked mechanism via which information can be encoded and decoded in animal communicative exchanges.

Background: Myocarditis and myopericarditis are well described adverse events of special interest (AESI) following COVID-19 vaccinations. Although reports are reassuring regarding initial clinical outcomes, information about longer term outcomes remains limited. We aimed to further this knowledge and report outcomes to 6 months post diagnosis from a single population cohort.Methods: Reports of myocarditis following COVID-19 vaccination were followed up by SAEFVIC (Surveillance of Adverse Events Following Vaccination in the Community), the state-wide vaccine safety service for Victoria, Australia. Confirmed myocarditis cases (Brighton Collaboration Criteria levels 1-3) were followed up via surveys at 1, 3 and 6 months post symptom onset. Responses received between 22 February 2021 and 30 September 2022 were analysed. Results: 87.5% (N = 182) of eligible participants completed at least 1 survey report. 377 reports were analysed. 76.9% of completed reports were from male patients. The median age of patients was 21 years [IQR: 16 to 32]. 54.8% (n = 74) of survey reports at 6 months, reported ongoing symptoms. At all follow-up time points, females were significantly more likely to have ongoing symptoms. At 6 months, 51.9% of male respondents reported symptom resolution compared to 22.6% of female patients (p = 0.002). Females were also more likely to continue medication and have ongoing exercise restrictions. However, males were significantly more likely to have higher initial peak troponin results and abnormal initial cardiac imaging investigations.Conclusions: There appears to be a significant proportion of patients who experience ongoing symptoms to 6 months post onset amongst patients that experience these AESI. Male patients were more likely to report earlier and more complete symptom recovery, despite significantly higher average initial peak troponin. This difference in phenotypic presentation in females compared to males warrants further investigation and there is a need for longer term follow up data.

Introduction The increasing availability of electronic health records (EHRs), including not only medical records but also imaging DICOMs, offers opportunities for enhanced patient care through automated case detection and surveillance. Hypothesis We hypothesized that artificial intelligence (AI) automation could be used to identify cases of heart failure (HF) and classify the type of HF (with preserved or reduced ejection fraction [HFpEF or HFrEF]) from routine EHR surveillance. Methods We performed a population-based cohort study of EHR data covering the population of Tayside and Fife since 1993, covering ∼20% of the Scottish population. Using a patient-specific identifier, linkage to other clinical datasets was possible, including community-dispensed prescriptions, echocardiography DICOM images, hospital admissions (Scottish Morbidity Record), and mortality data (General Registry Office). A combination of keyword search of medical records and AI automated reading of stored echocardiographic DICOM images (Us2.ai) was used to identify patients with HFpEF, HFrEF and controls without HF. Verification of the final diagnosis was performed through manual review of medical records, measurement of natriuretic peptides in stored blood samples of identified patients, and comparison of clinical outcomes among groups. Results Among 3680 patient records with linkage to echocardiographic DICOMs and blood samples, we identified 236 patients with HFpEF, 156 with HFrEF, and 185 controls (Table). Compared to HFrEF, patients with HFpEF were older, more often women and had less coronary artery disease. Compared to controls, patients with HFpEF and HFrEF had greater LV mass, higher mitral E/e’ ratio, higher pulmonary artery systolic pressure, more impaired LV strain and RV dysfunction. While majority of patients with HFrEF were on guideline-directed medical therapy, a gap in treatment was identified for mineralocorticoid receptor antagonists. NT-proBNP was higher in HFpEF, and even higher in HFrEF, compared to controls. During a median follow up time of 1089 days, 39% of HFpEF and 63% of HFrEF experienced hospitalization or death, compared to only 5% of controls. Conclusions We demonstrate the feasibility of AI-automated detection and classification of HF from routine surveillance of electronic health data, yielding cohorts with clinical and echocardiographic characteristics similar to epidemiologic studies, with raised natriuretic peptides and poor outcomes expected in these patient populations. Such AI-assisted electronic surveillance may have application in automated monitoring of clinical records for early disease detection, treatment quality improvement initiatives, and case finding for clinical trials.

PURPOSE: A hypertensive response to exercise (HRE) recorded during clinical exercise testing is independently associated with cardiovascular disease (CVD), but its interpretation may be clouded by functional capacity (fitness). Type-2 diabetes (T2DM) is associated with increased prevalence of HRE, but whether this confers additional CVD risk in T2DM when HRE is considered relative to fitness has never been determined and was the aim of this study. METHODS: Clinical exercise test records were analysed from 14,449 people (aged 52.4 ± 13.5 years, 58.7% male) who completed the Bruce treadmill protocol (stages 1-4, and peak) at 6 Australian hospitals. Records (including BP) were linked to administrative health datasets (hospital and emergency admissions, death register) to define clinical characteristics, classify T2DM (n = 1,321) vs. no-T2DM (n = 13,128) and determine the primary outcome of CVD events and death (mean follow-up, 56 ± 33 months, n = 1452 events). To consider exercise systolic BP relative to fitness, systolic BP was divided by peak METs and defined as HRE if values were ≥ 90th percentile for each exercise test stage. Survival analysis using cox-proportional hazards was undertaken to compare outcome rates across strata of those with (+) and without (-) HRE and T2DM. RESULTS: Compared to HRE- and T2DM- (reference), there was a stepwise increase in age and sex adjusted CVD event and death rate across the strata (HRE+ and T2DM-, HRE- and T2DM+, HRE+ and T2DM+), with those HRE+ and T2DM+ showing the highest risk at exercise test stage 1 (HR 1.95, 95%CI: 1.61-2.35), stage 2 (HR 2.05, 95%CI: 1.71-2.47), stage 3 (HR 2.52, 95%CI: 2.12-3.00), stage 4 (HR 3.04, 95%CI: 2.88-3.72) and at peak exercise (HR 1.71, 95%CI: 1.39-2.10). These associations were stronger than if HRE was not considered relative to fitness and persisted when the sample was restricted to those without a history of CVD at baseline (P < 0.01 at stages 1-4 and peak exercise). CONCLUSIONS: When the systolic BP response to exercise testing is considered relative to fitness, those with T2DM and HRE have increased risk of CVD events and death compared to those without. This suggests that clinicians supervising exercise testing should be alert to HRE and impaired functional capacity in people with T2DM and optimise therapy to address heightened CVD risk.

Background: Deep learning (DL)-based interpretation of echocardiographic images can help create pragmatic cohort studies to validate novel biomarkers. In this study, we have characterised biomarkers implicated in heart failure (HF) pathophysiology across the ejection fraction (EF) range in a DL-supported pragmatic cohort study. Methods: We used electronic health record data from Tayside, representing 20% of the Scottish population, between 1993 and 2021. Utilising record linkage to DL automated reading of echocardiographic DICOM images, we identified patients with HFrEF or HFpEF and patients without HF. We then linked identified patients to available plasma samples from the Go-SHARE BioBank. We analysed multi-panel biomarkers, such as NT-proBNP, high-sensitivity cardiac troponin-T (hs-cTnT), growth differentiation factor-15 (GDF-15), insulin-like growth factor-binding protein-7 (IGFBP-7), bone morphogenetic protein-10 (BMP-10), Dickkopf WNT Signaling Pathway Inhibitor-3 (DKK-3), fibroblast growth factor-23 (FGF-23), angiopoietin-2 (Ang2), and fatty acid-binding protein-3 (FABP-3), all with electrochemiluminescence immunoassays (Roche Diagnostics, Germany). Results: We identified 236 patients with HFpEF, 156 with HFrEF, and 185 patients without HF with available plasma samples from 3680 patient records linked to echocardiographic DICOMs and blood samples. Patients with HFrEF and HFpEF had significantly higher median values of hs-cTnT, GDF-15, NT-proBNP, IGFBP-7, DKK-3, and FGF-23 than controls. The diagnostic accuracy (AUC) of NT-proBNP, hs-cTnT, GDF-15, IGFBP-7, and FABP-3 was >0.8 for identifying patients with HFrEF or HFpEF from controls. DL-algorithm-based interpretation of DICOM images provided further coverage of echocardiographic parameters relevant for diagnosis of HF subtypes. All biomarkers were associated with all-cause mortality and HF-related hospitalisation during a median follow-up of 1089 days. Conclusions: In this population-based study, we demonstrated a novel approach utilising a bioresource linked to a DL-supported pragmatic study to explore biomarkers in HF and demonstrated that multiple biomarkers to have diagnostic and prognostic significance for patients with HFrEF and HFpEF.

Aims Experimental studies demonstrate protective effects of doxycycline on myocardial ischaemia-reperfusion injury. The trial investigated whether doxycycline administered prior to reperfusion in patients presenting with ST-elevation myocardial infarction (STEMI) reduces infarct size (IS) and ameliorates adverse left ventricular (LV) remodelling. Methods and results In this randomized, double-blind, placebo-controlled trial, patients presenting with STEMI undergoing primary percutaneous coronary intervention (PPCI) were randomized to either intravenous doxycycline or placebo prior to reperfusion followed by 7 days of oral doxycycline or placebo. The primary outcome was final IS adjusted for area-at-risk (fIS/AAR) measured on two cardiac magnetic resonance scans similar to 6 months apart. Of 103 participants, 50 were randomized to doxycycline and 53 to placebo and were matched for age (59 +/- 12 vs. 60 +/- 10 years), male sex (92% vs. 79%), diabetes mellitus (26% vs. 11%) and left anterior descending artery occlusion (50% vs. 49%), all P > 0.05. Patients treated with doxycycline had a trend for larger fIS/AAR [0.79 (0.5-0.9) vs. 0.61 (0.47-0.76), P = 0.06], larger fIS at 6 months [18.8% (12-26) vs. 13.6% (11-21), P = 0.08], but similar acute IS [21.7% (17-34) vs. 19.4% (14-27), P = 0.19] and AAR [26% (20-36) vs. 24.7% (16-31), P = 0.22] compared with placebo. Doxycycline did not ameliorate adverse LV remodelling [%Delta end-diastolic volume index, 1.1% (-3.8-8.4) vs. -1.34% (-6.1-5.8), P = 0.42] and was independently associated with larger fIS (regression coefficient = 0.175, P = 0.03). Conclusion Doxycycline prior to PPCI neither reduced IS acutely or at six months nor attenuated adverse LV remodelling. These data raise safety concerns regarding doxycycline use in STEMI for infarct modulation and healing.

Background: Patients undergoing heart transplant are at high risk for postoperative vasoplegia. Despite its frequency and association with poor clinical outcomes, there remains no consensus definition for vasoplegia, and the predisposing risk factors for vasoplegia remain unclear. Accordingly, the aim of this study was to evaluate the prevalence, predictors, and clinical outcomes associated with vasoplegia in a contemporary cohort of patients undergoing heart transplantation. Methods: This was a retrospective cohort study of patients undergoing heart transplantation from January 2015 to December 2019. A binary definition of vasoplegia of a cardiac index of 2.5 L/min/m2 or greater and requirement for norepinephrine (>5 mg/min), epinephrine (>4 mg/min), or vasopressin (>1 unit/h) to maintain a mean arterial blood pressure of 65 mm Hg, for 6 consecutive hours during the first 48 hours postoperatively, was used in determining prevalence. Given the relatively low threshold for the binary definition of vasoplegia, patients were divided into tertiles based on their cumulative vasopressor requirement in the 48 hours following transplant. Outcomes included all-cause mortality, intubation time, intensive care unit length of stay, and length of total hospitalization. Results: After exclusion of patients with primary cardiogenic shock, major bleeding, or overt sepsis, data were collected on 95 eligible patients. By binary definition, vasoplegia incidence was 66.3%. We separately stratified by actual vasopressor requirement tertile (high, intermediate, low). Stratified by tertile, patients with vasoplegia were older (52.7 +/- 10.2 vs 46.8 +/- 12.7 vs 44.4 +/- 11.3 years, P = .02), with higher rates of chronic kidney disease (18.8% vs 32.3% vs 3.1%, P = .01) and were more likely to have been transplanted from left ventricular assist device support (n =42) (62.5% vs 32.3% vs 37.5%, P = .03). Cardiopulmonary bypass time was prolonged in those that developed vasoplegia (155 min [interquartile range 135-193] vs 131 min [interquartile range 117-152] vs 116 min [interquartile range 102-155], P = .003). Intubation time and length of intensive care unit and hospital stay were significantly increased in those that developed vasoplegia; however, this difference did not translate to a significant increase in all-cause mortality at 30 days or 1 year. Conclusions: Vasoplegia occurs at a high rate after heart transplantation. Older age, chronic kidney disease, mechanical circulatory support, and prolonged bypass time are all associated with vasoplegia; however, this study did not demonstrate an associated increase in all-cause mortality Lay Summary: Patients undergoing heart transplantation are at high risk of vasoplegia, a condition defined by low blood pressure despite normal heart function. We found that vasoplegia was common after heart transplant, occurring in 60%-70% of patients after heart transplant after excluding those with other causes for low blood pressure. Factors implicated included age, poor kidney function, prolonged cardiopulmonary bypass time and preoperative left ventricular assist device support. We found no increased risk of death in patients with vasoplegia despite longer lengths of stay in intensive care and in hospital. (J Cardiac Fail 2022;28:617-626)

Amyloidosis is a collection of diseases caused by the misfolding of proteins that aggregate into insoluble amyloid fibrils and deposit in tissues. While these fibrils may aggregate to form insignificant localised deposits, they can also accumulate in multiple organs to the extent that amyloidosis can be an immediately life-threatening disease, requiring urgent treatment. Recent advances in diagnostic techniques and therapies are dramatically changing the disease landscape and patient prognosis. Delays in diagnosis and treatment remain the greatest challenge, necessitating physician awareness of the common clinical presentations that suggest amyloidosis. The most common types are transthyretin (ATTR) amyloidosis followed by immunoglobulin light-chain (AL) amyloidosis. While systemic AL amyloidosis was previously considered a death sentence with no effective therapies, significant improvement in patient survival has occurred over the past 2 decades, driven by greater understanding of the disease process, risk-adapted adoption of myeloma therapies such as proteosome inhibitors (bortezomib) and monoclonal antibodies (daratumumab) and improved supportive care. ATTR amyloidosis is an underdiagnosed cause of heart failure. Technetium scintigraphy has made noninvasive diagnosis much easier, and ATTR is now recognised as the most common type of amyloidosis because of the increased identification of age-related ATTR. There are emerging ATTR treatments that slow disease progression, decrease patient hospitalisations and improve patient quality of life and survival. This review aims to update physicians on recent developments in amyloidosis diagnosis and management and to provide a diagnostic and treatment framework to improve the management of patients with all forms of amyloidosis.

We present the case of acute myocardial infarction secondary to spontaneous coronary artery dissection in a patient 2 weeks post orthotopic heart transplantation. (Level of Difficulty: Advanced.).

Trivers and Willard proposed that female mammals should adjust their investment in male versus female offspring relative to their ability to produce high-quality offspring. We tested whether litter size–sex ratio trade-offs predicted by Adaptive Sex Allocation (ASA) theory occur among Richardson’s ground squirrel (Urocitellus richardsonii) dams over 10 distinct breeding years in a population where individuals experienced variability in food availability and habitat disruption. Litters of primiparous dams became increasingly female-biased with increasing litter size, but that trend waned among second litters born to dams, and reversed among third litters, with larger litters becoming more male-biased, suggesting that ASA is a product of interacting selection pressures. Trade-offs were not associated with habitat disruption, the availability of supplementary food, or dam age. An association between habitat disruption and male-biased sex ratios, the prevalence of litter size–sex ratio trade-offs and placental scar counts exceeding the number of juveniles at weaning in our population, but not in a geographically distinct population of conspecifics exposed to different environmental conditions reveal that the expression of ASA varies among populations and among years within populations, illustrating the conditional nature of ASA.

Hibernating ground squirrels rely on a short active period for breeding and mass accrual, and are thus vulnerable to extreme climate events that affect key periods in their annual cycle. Here, we document how a heatwave in March 2012 led to a phenological mismatch between sexes in Richardson's ground squirrels (Urocitellus richardsonii). Females emerged from hibernation and commenced breeding earlier in 2012 relative to average female emergence. Although males had descended testes and pigmented scrota, it appeared that not all males were physiologically prepared to breed since 58.6% of males had non-motile sperm when breeding commenced. Body condition, relative testes size, and the relative size of accessory glands were significant predictors of sperm motility. Males with non-motile sperm had smaller accessory glands than males with motile sperm. There was no decrease in the number of juveniles that emerged in 2012 or female yearlings recruited in 2013, nor did juveniles emerge later than other years. The impact of this heatwave on male ground squirrels emphasizes the importance of assessing the consequences of climate change on the breeding success of hibernating species in both sexes, since the different sensitivity to external cues for emergence led to a mismatch in timing under this event.

Objective: Exaggerated exercise blood pressure (EEBP) during clinical exercise testing is associated with elevated cardiovascular disease (CVD) risk. Type-2 diabetes (T2DM) is thought to be associated with higher prevalence of EEBP, but this has never been determined in a large clinical population, which was the aim of this study. Design and method: Clinical exercise test records were analysed from 15,994 people (mean age 53 ± 13 years, 59% male) referred for the Bruce treadmill protocol (stages 1–4 + peak) at 4 Australian public hospitals. Exercise records including blood pressure (BP) were linked to administrative datasets (hospital and emergency admissions) to define clinical characteristics and classify prior history of T2DM (n = 1,345) vs. no-T2DM (n = 14,649). EEBP was defined > 90th centile for each exercise stage. Exercise BP was regressed on T2DM history, adjusted to consider CVD risk factors. Results: EEBP prevalence (stage-1: + 4.1%; stage-2: + 4.4%; stage-3: + 4.9%; stage-4: + 4.8%; peak: + 1.9%, P < 0.05 respectively) and exercise systolic BP (stage-1: + 4.25, stage-2: + 4.52, stage-3: + 4.43, stage-4: + 3.08, peak: + 0.75 mmHg, P < 0.05 respectively) were higher across all exercise stages in T2DM vs. no-T2DM. However, all differences were abolished by adjustment for either: age, sex, peak workload, CVD history, or pre-exercise BP. Restricting analyses to those with normal pre-exercise BP (<140/90 or < 130/90 mmHg) revealed no differences in exercise BP or EEBP prevalence between T2DM and no-T2DM. Conclusions: This is the first study to confirm higher prevalence of EEBP in T2DM, but this is explained by accompanying CVD risk factors. Identification of EEBP should prompt aggressive CVD risk factor modification in T2DM.